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Functional Interplay between Histone H2B ADP-Ribosylation and Phosphorylation Controls Adipogenesis.

Publication ,  Journal Article
Huang, D; Camacho, CV; Setlem, R; Ryu, KW; Parameswaran, B; Gupta, RK; Kraus, WL
Published in: Mol Cell
September 17, 2020

Although ADP-ribosylation of histones by PARP-1 has been linked to genotoxic stress responses, its role in physiological processes and gene expression has remained elusive. We found that NAD+-dependent ADP-ribosylation of histone H2B-Glu35 by small nucleolar RNA (snoRNA)-activated PARP-1 inhibits AMP kinase-mediated phosphorylation of adjacent H2B-Ser36, which is required for the proadipogenic gene expression program. The activity of PARP-1 on H2B requires NMNAT-1, a nuclear NAD+ synthase, which directs PARP-1 catalytic activity to Glu and Asp residues. ADP-ribosylation of Glu35 and the subsequent reduction of H2B-Ser36 phosphorylation inhibits the differentiation of adipocyte precursors in cultured cells. Parp1 knockout in preadipocytes in a mouse lineage-tracing genetic model increases adipogenesis, leading to obesity. Collectively, our results demonstrate a functional interplay between H2B-Glu35 ADP-ribosylation and H2B-Ser36 phosphorylation that controls adipogenesis.

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Published In

Mol Cell

DOI

EISSN

1097-4164

Publication Date

September 17, 2020

Volume

79

Issue

6

Start / End Page

934 / 949.e14

Location

United States

Related Subject Headings

  • RNA, Small Nucleolar
  • Poly (ADP-Ribose) Polymerase-1
  • Phosphorylation
  • Mice
  • Histones
  • Gene Expression Regulation, Developmental
  • Developmental Biology
  • DNA Damage
  • Cell Line
  • Animals
 

Citation

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Huang, D., Camacho, C. V., Setlem, R., Ryu, K. W., Parameswaran, B., Gupta, R. K., & Kraus, W. L. (2020). Functional Interplay between Histone H2B ADP-Ribosylation and Phosphorylation Controls Adipogenesis. Mol Cell, 79(6), 934-949.e14. https://doi.org/10.1016/j.molcel.2020.08.002
Huang, Dan, Cristel V. Camacho, Rohit Setlem, Keun Woo Ryu, Balaji Parameswaran, Rana K. Gupta, and W Lee Kraus. “Functional Interplay between Histone H2B ADP-Ribosylation and Phosphorylation Controls Adipogenesis.Mol Cell 79, no. 6 (September 17, 2020): 934-949.e14. https://doi.org/10.1016/j.molcel.2020.08.002.
Huang D, Camacho CV, Setlem R, Ryu KW, Parameswaran B, Gupta RK, et al. Functional Interplay between Histone H2B ADP-Ribosylation and Phosphorylation Controls Adipogenesis. Mol Cell. 2020 Sep 17;79(6):934-949.e14.
Huang, Dan, et al. “Functional Interplay between Histone H2B ADP-Ribosylation and Phosphorylation Controls Adipogenesis.Mol Cell, vol. 79, no. 6, Sept. 2020, pp. 934-949.e14. Pubmed, doi:10.1016/j.molcel.2020.08.002.
Huang D, Camacho CV, Setlem R, Ryu KW, Parameswaran B, Gupta RK, Kraus WL. Functional Interplay between Histone H2B ADP-Ribosylation and Phosphorylation Controls Adipogenesis. Mol Cell. 2020 Sep 17;79(6):934-949.e14.
Journal cover image

Published In

Mol Cell

DOI

EISSN

1097-4164

Publication Date

September 17, 2020

Volume

79

Issue

6

Start / End Page

934 / 949.e14

Location

United States

Related Subject Headings

  • RNA, Small Nucleolar
  • Poly (ADP-Ribose) Polymerase-1
  • Phosphorylation
  • Mice
  • Histones
  • Gene Expression Regulation, Developmental
  • Developmental Biology
  • DNA Damage
  • Cell Line
  • Animals